Antimotility agent

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Antimotility agents are drugs used to alleviate the symptoms of diarrhea. These include loperamide (Imodium), bismuth subsalicylate (Pepto-Bismol), [1] diphenoxylate with atropine (Lomotil), and opiates such as paregoric, tincture of opium, codeine, and morphine. In diarrhea caused by invasive pathogens such as Salmonella , Shigella , and Campylobacter , the use of such agents has generally been strongly discouraged, though evidence is lacking that they are harmful when administered in combination with antibiotics in Clostridium difficile cases. [2] Use of antimotility agents in children and the elderly has also been discouraged in treatment of EHEC (Shiga-like toxin producing Escherichia coli ) due to an increased rate of hemolytic uremic syndrome. [3]

Contents

Loperamide (Imodium)

Mechanism of action

Loperamide is a μ-opioid receptor agonist. [4] By binding to μ-opioid receptors, loperamide inhibits acetylcholine release and decreases excitation of neurons in the myenteric plexus, which leads to a decrease in peristalsis. [4] Decreasing intestinal motility prolongs the transit time of food content through the digestive tract, which allows for more fluid absorption; thereby alleviating diarrhea symptoms and improving stool consistency and frequency. [4]

Unlike other opiates, loperamide does not cross the blood brain barrier, so there is minimal risk for abuse. [5]

Adverse effects

Side effects of use of anti-motility agents include:

Contraindications

Contraindications include:

Drug interactions

CYP3A4 inhibitors, such as erythromycin, fluconazole, ketoconazole, quinidine, and ritonavir, increase plasma levels of loperamide [7]

Bismuth subsalicylate (Pepto-Bismol)

Mechanism of action

Bismuth subsalicylate (BSS) has both antibacterial and anti-secretory actions that help with diarrhea. [1] Once in the gut, BSS gets broken down into bismuth and salicylic acid. [1] Bismuth produces other bismuth salts, which blocks the binding and proliferation of bacteria in stomach mucosal cells, leading to a decrease in inflammation in the intestine. [9] Also, BSS inhibits cyclooxygenase enzyme and leads to a decrease in the production of prostaglandins, which are compounds that increase intestinal inflammation and motility. [1] Lastly, this antidiarrheal agent enhances fluid reabsorption, which helps improve diarrhea symptoms and stool consistency. [1]

Adverse effects

Adverse effects include:

Contraindications

Contraindications include:

Drug interactions

Drug interactions may occur with: [1]

See also

Related Research Articles

An anti-diarrheal drug is any medication which provides symptomatic relief for diarrhea.

<span class="mw-page-title-main">Diarrhea</span> Loose or liquid bowel movements

Diarrhea, also spelled diarrhoea or diarrhœa, is the condition of having at least three loose, liquid, or watery bowel movements in a day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin with loss of the normal stretchiness of the skin and irritable behaviour. This can progress to decreased urination, loss of skin color, a fast heart rate, and a decrease in responsiveness as it becomes more severe. Loose but non-watery stools in babies who are exclusively breastfed, however, are normal.

<span class="mw-page-title-main">Shigellosis</span> Medical condition

Shigellosis is an infection of the intestines caused by Shigella bacteria. Symptoms generally start one to two days after exposure and include diarrhea, fever, abdominal pain, and feeling the need to pass stools even when the bowels are empty. The diarrhea may be bloody. Symptoms typically last five to seven days and it may take several months before bowel habits return entirely to normal. Complications can include reactive arthritis, sepsis, seizures, and hemolytic uremic syndrome.

<span class="mw-page-title-main">Loperamide</span> Medicine used to reduce diarrhea

Loperamide, sold under the brand name Imodium, among others, is a medication of the opioid receptor agonist class used to decrease the frequency of diarrhea. It is often used for this purpose in irritable bowel syndrome, inflammatory bowel disease and short bowel syndrome. It is not recommended for those with blood in the stool, mucus in the stool, or fevers. The medication is taken by mouth.

<i>Clostridioides difficile</i> infection Disease caused by C. difficile bacteria

Clostridioides difficile infection, also known as Clostridium difficile infection, is a symptomatic infection due to the spore-forming bacterium Clostridioides difficile. Symptoms include watery diarrhea, fever, nausea, and abdominal pain. It makes up about 20% of cases of antibiotic-associated diarrhea. Antibiotics can contribute to detrimental changes in gut microbiota; specifically, they decrease short-chain fatty acid absorption which results in osmotic, or watery, diarrhea. Complications may include pseudomembranous colitis, toxic megacolon, perforation of the colon, and sepsis.

<span class="mw-page-title-main">Enteritis</span> Intestinal inflammatory disease

Enteritis is inflammation of the small intestine. It is most commonly caused by food or drink contaminated with pathogenic microbes, such as Serratia, but may have other causes such as NSAIDs, radiation therapy as well as autoimmune conditions like coeliac disease. Symptoms include abdominal pain, cramping, diarrhoea, dehydration, and fever. Related diseases of the gastrointestinal system involve inflammation of the stomach and large intestine.

<span class="mw-page-title-main">Hemolytic–uremic syndrome</span> Group of blood disorders related to bacterial infection

Hemolytic–uremic syndrome (HUS) is a group of blood disorders characterized by low red blood cells, acute kidney injury, and low platelets. Initial symptoms typically include bloody diarrhea, fever, vomiting, and weakness. Kidney problems and low platelets then occur as the diarrhea progresses. Children are more commonly affected, but most children recover without permanent damage to their health, although some children may have serious and sometimes life-threatening complications. Adults, especially the elderly, may present a more complicated presentation. Complications may include neurological problems and heart failure.

<span class="mw-page-title-main">Gastroenteritis</span> Inflammation of the stomach and small intestine

Gastroenteritis, also known as infectious diarrhea or simply as gastro, is an inflammation of the gastrointestinal tract including the stomach and intestine. Symptoms may include diarrhea, vomiting, and abdominal pain. Fever, lack of energy, and dehydration may also occur. This typically lasts less than two weeks. Although it is not related to influenza, in the U.S. and U.K., it is sometimes called the "stomach flu".

<span class="mw-page-title-main">Bismuth subsalicylate</span> Antacid medication

Bismuth subsalicylate, sold generically as pink bismuth and under brand names including Pepto-Bismol, Pepti-Calm and BisBacter, is a medication used to treat temporary discomfort of the stomach and gastrointestinal tract, such as nausea, heartburn, indigestion, upset stomach, and diarrhea.

<span class="mw-page-title-main">Travelers' diarrhea</span> Stomach and intestinal infection

Travelers' diarrhea (TD) is a stomach and intestinal infection. TD is defined as the passage of unformed stool while traveling. It may be accompanied by abdominal cramps, nausea, fever, headache and bloating. Occasionally bloody diarrhea may occur. Most travelers recover within three to four days with little or no treatment. About 12% of people may have symptoms for a week.

<span class="mw-page-title-main">Thrombotic microangiopathy</span> Medical condition

Thrombotic microangiopathy (TMA) is a pathology that results in thrombosis in capillaries and arterioles, due to an endothelial injury. It may be seen in association with thrombocytopenia, anemia, purpura and kidney failure.

<span class="mw-page-title-main">Rifaximin</span> Antibiotic medication

Rifaximin, is a non-absorbable, broad spectrum antibiotic mainly used to treat travelers' diarrhea. It is based on the rifamycin antibiotics family. Since its approval in Italy in 1987, it has been licensed in over more than 30 countries for the treatment of a variety of gastrointestinal diseases like irritable bowel syndrome, and hepatic encephalopathy. It acts by inhibiting RNA synthesis in susceptible bacteria by binding to the RNA polymerase enzyme. This binding blocks translocation, which stops transcription. It is marketed under the brand name Xifaxan by Salix Pharmaceuticals.

Antibiotic-associated diarrhea (AAD) results from an imbalance in the colonic microbiota caused by antibiotics. Microbiotal alteration changes carbohydrate metabolism with decreased short-chain fatty acid absorption and an osmotic diarrhea as a result. Another consequence of antibiotic therapy leading to diarrhea is overgrowth of potentially pathogenic organisms such as Clostridium difficile. It is defined as frequent loose and watery stools with no other complications.

<span class="mw-page-title-main">Racecadotril</span> Chemical compound

Racecadotril, also known as acetorphan, is an antidiarrheal medication which acts as a peripheral enkephalinase inhibitor. Unlike other opioid medications used to treat diarrhea, which reduce intestinal motility, racecadotril has an antisecretory effect — it reduces the secretion of water and electrolytes into the intestine. It is available in France and other European countries as well as most of South America and some South East Asian countries, but not in the United States. It is sold under the tradename Hidrasec, among others. Thiorphan is the active metabolite of racecadotril, which exerts the bulk of its inhibitory actions on enkephalinases.

Chronic diarrheaof infancy, also called toddler's diarrhea, is a common condition typically affecting up to 1.7 billion children between ages 6–30 months worldwide every year, usually resolving by age 4. According to the World Health Organization (WHO), diarrheal disease is the second greatest cause of death in children 5 years and younger. Diarrheal disease takes the lives of 525,000 or more children per year. Diarrhea is characterized as the condition of passing of three or more loose or watery bowel movements within a day sometimes with undigested food visible. Diarrhea is separated into three clinical categories; acute diarrhea may last multiple hours or days, acute bloody diarrhea, also known as dysentery, and finally, chronic or persistent diarrhea which lasts 2–4 weeks or more. There is normal growth with no evidence of malnutrition in the child experiencing persistent diarrhea. In chronic diarrhea there is no evidence of blood in the stool and there is no sign of infection. The condition may be related to irritable bowel syndrome. There are various tests that can be performed to rule out other causes of diarrhea that don't fall under the chronic criteria, including blood test, colonoscopy, and even genetic testing. Most acute or severe cases of diarrhea have treatment guidelines revolving around prescription or non prescription medications based on the cause, but the treatment protocols for chronic diarrhea focus on replenishing the body with lost fluids and electrolytes, because there typically isn't a treatable cause.

<span class="mw-page-title-main">Crofelemer</span> Pharmaceutical drug

Crofelemer is an antidiarrheal indicated for the symptomatic relief of non-infectious diarrhea in adult patients with HIV/AIDS on antiretroviral therapy. Other possible uses include diarrhea in children, acute infectious diarrhea, and diarrhea in patients with irritable bowel syndrome. It is a purified oligomeric proanthocyanidin from "dragon's blood", the sap of the South American tree Croton lechleri.

Atypical hemolytic uremic syndrome (aHUS), also known as complement-mediated hemolytic uremic syndrome, is an extremely rare, life-threatening, progressive disease that frequently has a genetic component. In most cases it can be effectively controlled by interruption of the complement cascade. Particular monoclonal antibodies, discussed later in the article, have proven efficacy in many cases.

<i>Clostridioides difficile</i> Species of bacteria

Clostridioides difficile is a bacterium known for causing serious diarrheal infections, and may also cause colon cancer. It is known also as C. difficile, or C. diff, and is a Gram-positive species of spore-forming bacteria. Clostridioides spp. are anaerobic, motile bacteria, ubiquitous in nature and especially prevalent in soil. Its vegetative cells are rod-shaped, pleomorphic, and occur in pairs or short chains. Under the microscope, they appear as long, irregular cells with a bulge at their terminal ends. Under Gram staining, C. difficile cells are Gram-positive and show optimum growth on blood agar at human body temperatures in the absence of oxygen. C. difficile is catalase- and superoxide dismutase-negative, and produces up to three types of toxins: enterotoxin A, cytotoxin B and Clostridioides difficile transferase. Under stress conditions, the bacteria produce spores that are able to tolerate extreme conditions that the active bacteria cannot tolerate.

<span class="mw-page-title-main">Opioid withdrawal</span> Withdrawal symptoms of opiates

Opioid withdrawal is a set of symptoms arising from the sudden withdrawal or reduction of opioids where previous usage has been heavy and prolonged. Signs and symptoms of withdrawal can include drug craving, anxiety, restless legs, nausea, vomiting, diarrhea, sweating, and an increased heart rate. Opioid use triggers a rapid adaptation in cellular signalling pathways that means, when rapidly withdrawn, there can be adverse physiological effects. All opioids, both recreational drugs and medications, when reduced or stopped, can lead to opioid withdrawal symptoms. When withdrawal symptoms are due to recreational opioid use, the term opioid use disorder is used, whereas when due to prescribed medications, the term prescription opioid use disorder is used. Opioid withdrawal can be helped by the use of opioid replacement therapy, and symptoms may be relieved by the use of medications including lofexidine and clonidine.

Checkpoint inhibitor induced colitis is an inflammatory condition affecting the colon (colitis), which is caused by cancer immunotherapy. Symptoms typically consist of diarrhea, abdominal pain and rectal bleeding. Less commonly, nausea and vomiting may occur, which may suggest the present of gastroenteritis. The severity of diarrhea and colitis are graded based on the frequency of bowel movements and symptoms of colitis, respectively.

References

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